Intercept, Annovis and Biohaven Advance Late Phase Trials

Phase III Good News for Intercept, Annovis and Biohaven

Several biopharma companies reported late-stage Phase III clinical trial success Thursday. Here’s a look.

Positive Pivotal NASH Data Sets Intercept Up for NDA Resubmission

Intercept Pharmaceuticals reported positive topline results from a new interim analysis of its ongoing pivotal Phase III REGENERATE trial. The study is evaluating obeticholic acid (OCA) in liver fibrosis (scarring) due to nonalcoholic steatohepatitis (NASH). NASH is similar to cirrhosis of the liver but occurs in people who drink little or no alcohol. It is a kind of fatty liver disease.

This is the second analysis where OCA hit the primary endpoint for the intent-to-treat population in REGENERATE. Based on the results, the company plans to re-submit its New Drug Application to the U.S. Food and Drug Administration for OCA in liver fibrosis due to NASH. In this new analysis, 22.4% of patients receiving once-daily oral OCA 25 mg hit the primary endpoint of achieving at least one stage of fibrosis improvement with no worsening of NASH at the 18th month on liver biopsy. This compared to 9.6% in the placebo group. The safety profile was manageable, with serious adverse events and deaths generally balanced across the OCA and placebo cohorts.

“Achieving a statistically significant histology endpoint has proven to be an extremely high bar in clinical trials for NASH,” Jerry Durso, president and chief executive officer of Intercept said. “We are thrilled that OCA has demonstrated consistent improvement in fibrosis based on a second methodology and we now have two positive, statistically significant results for this primary endpoint from our pivotal REGENERATE trial.”

The FDA issued a Complete Response Letter for the company’s first NDA for OCA for this indication in June 2020. The agency indicated that the predicted benefit of the drug based on a surrogate histopathologic endpoint was uncertain and didn’t sufficiently outweigh the potential risks of the drug.

Annovis' Phase III Parkinson’s Study is Full Speed Ahead

Annovis Bio announced that the FDA had given it a green light to initiate a Phase III trial of buntanetap for Parkinson’s disease (PD). The regulator approved the final protocol, clinical development and Annovis’ new large-scale batch of good manufacturing practice (GMP) material. It also found that toxicology studies in animals were safe and adequate to support long-term human studies that could last decades.

The regulator had requested an amendment to the development plan after submitting a comprehensive data package in animals and humans, as well as manufacturing data and data gathered over several years for its Alzheimer’s disease program that was related to the Parkinson’s program.

Buntanetap is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs). Its method of action leads to lower levels of neurotoxic proteins and thus less toxicity to the brain.

“We are pleased that the FDA has approved our clinical trial design in early PD patients and called it a well-designed study,” Maria L. Maccecchini, Ph.D., founder, president and chief executive officer of Annovis said. “The positive FDA review affirms the company’s path to securing approval for buntanetap to treat neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases, with longer treatment regimens. With this FDA notice in hand, we are thrilled to start recruiting for the U.S. clinical trial soon, expected later this summer.”

Biohaven Enrolls First Patient in Phase III SMA Study

Biohaven Pharma enrolled the first patient in its Phase III study of taldefgrobep alfa in Spinal Muscular Atrophy (SMA). The drug is an investigational, muscle-targeted recombinant protein that is designed to improve muscle mass and strength in people with SMA when combined with other approved therapies. The drug targets myostatin, a natural protein that limits skeletal muscle growth. The company expects to enroll about 180 patients in the study.

SMA is a rare genetic neurodegenerative disorder marked by loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness that is often fatal. It is usually diagnosed in young children. It is caused by not enough production of the SMN (survival of motor neuron) protein and encoded by two genes, SMN1 and SMN2.

“This is an important milestone for the taldefgrobep program and for people living with SMA,” Dr. Irfan Qureshi, M.D., senior vice president, neurology at Biohaven said. “There have been great strides in advancing therapeutics in this challenging disease. Yet, there remains a significant unmet need to address the residual weakness and functional impairments, such as difficulty walking, that are caused by the disease.”

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